ArticleNeuro-oncology2021
Brain exposure of the ATM inhibitor AZD1390 in humans-a positron emission tomography study.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Evaluating "brain permeability": A critical issue for the development of therapeutic agents for primary and metastatic brain tumors.Neuro-oncology · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- The novel brain penetrant ataxia-telangiectasia mutated inhibitor WSD0628 provides robust radiosensitization of brain tumor patient-derived xenografts.Neuro-oncology · 2025Article
- Gene context drift identifies drug targets to mitigate cancer treatment resistance.Cancer cell · 2025Article
- Brain exposure of the mesenchymal-epithelial transition inhibitor savolitinib in nonhuman primates: A positron emission tomography study.The Journal of pharmacology and experimental therapeutics · 2025Article
- DNA Damage Response Regulation Alleviates Neuroinflammation in a Mouse Model of α-Synucleinopathy.Biomolecules · 2025Article
- Cancer Vulnerabilities Through Targeting the ATR/Chk1 and ATM/Chk2 Axes in the Context of DNA Damage.Cells · 2025Review
- The Development of ATM Inhibitors in Cancer Therapy.Targeted oncology · 2025Review
- Therapeutic Drug Distribution across the Mouse Brain Is Heterogeneous as Revealed by In Vivo, Spatially Resolved Aptamer-Based Sensing.ACS pharmacology & translational science · 2025Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.Cancer discovery · 2024Article
- ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- A new wave of innovations within the DNA damage response.Signal transduction and targeted therapy · 2023Review
- Discovery of [1,2,3]Triazolo[4,5-ACS medicinal chemistry letters · 2023Article
- Brain exposure of osimertinib in patients with epidermal growth factor receptor mutation non-small cell lung cancer and brain metastases: A positron emission tomography and magnetic resonance imaging study.Clinical and translational science · 2023Article
- Differences in DNA damage repair gene mutations between left- and right-sided colorectal cancer.Cancer medicine · 2023Article
- The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics.Annual review of cancer biology · 2023Article
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe protein kinase ataxia telangiectasia mutated (ATM) mediates cellular response to DNA damage induced by radiation. ATM inhibition decreases DNA damage repair in tumor cells and affects tumor growth. AZD1390 is a novel, highly potent, selective ATM inhibitor designed to cross the blood-brain barrier (BBB) and currently evaluated with radiotherapy in a phase I study in patients with brain malignancies. In the present study, PET was used to measure brain exposure of 11C-labeled AZD1390 after intravenous (i.v.) bolus administration in healthy subjects with an intact BBB.
methodsAZD1390 was radiolabeled with carbon-11 and a microdose (mean injected mass 1.21 µg) was injected in 8 male subjects (21-65 y). The radioactivity concentration of [11C]AZD1390 in brain was measured using a high-resolution PET system. Radioactivity in arterial blood was measured to obtain a metabolite corrected arterial input function for quantitative image analysis. Participants were monitored by laboratory examinations, vital signs, electrocardiogram, adverse events.
resultsThe brain radioactivity concentration of [11C]AZD1390 was 0.64 SUV (standard uptake value) and reached maximum 1.00% of injected dose at Tmax[brain] of 21 min (time of maximum brain radioactivity concentration) after i.v. injection. The whole brain total distribution volume was 5.20 mL*cm-3. No adverse events related to [11C]AZD1390 were reported.
conclusionsThis study demonstrates that [11C]AZD1390 crosses the intact BBB and supports development of AZD1390 for the treatment of glioblastoma multiforme or other brain malignancies. Moreover, it illustrates the potential of PET microdosing in predicting and guiding dose range and schedule for subsequent clinical studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.